Lower anti-Müllerian Hormone Levels Research Articles

Anti-Müllerian Hormone and OPU-ICSI Outcome in the Mare.

Simple SummaryThe in vitro production of equine embryos, using ovum pick-up (OPU) and intracytoplasmic sperm injection (ICSI), is gaining popularity for breeding sport horses. However, the results of this complicated procedure are variable and hard to predict. Therefore, the aim of this study was to evaluate anti-Müllerian hormone (AMH), a factor which has been linked to reproductive success in human and cattle, as an indicator of the OPU-ICSI outcome in horses. Therefore, for 103 mares subjected to commercial OPU-ICSI, the AMH level was measured in the blood at the moment of OPU and linked to the number of oocytes and embryos produced by ICSI. We found that mares with a high level of AMH gave rise to a better oocyte collection and a higher number of embryos. However, since mares with a low AMH value could also produce embryos, a single measurement of the AMH in the blood is not sufficient as an independent predictor of the OPU-ICSI outcome in the horse.Anti-Müllerian hormone (AMH) reflects the population of growing follicles and has been related to mammalian fertility. In the horse, clinical application of ovum pick-up and intracytoplasmic sperm injection (OPU-ICSI) is increasing, but results depend largely on the individuality of the mare. The aim of this study was to assess AMH as a predictor for the OPU-ICSI outcome in horses. Therefore, 103 mares with a total follicle count above 10 were included in a commercial OPU-ICSI session and serum AMH was determined using ELISA. Overall, the AMH level was significantly correlated with the number of aspirated follicles and the number of recovered oocytes (p < 0.001). Mares with a high AMH level (≥2.5 µg/L) yielded significantly greater numbers of follicles (22.9 ± 1.2), oocytes (13.5 ± 0.8), and blastocysts (2.1 ± 0.4) per OPU-ICSI session compared to mares with medium (1.5–2.5 µg/L) or low AMH levels (<1.5 µg/L), but no significant differences in blastocyst rates were observed. Yet, AMH levels were variable and 58% of the mares with low AMH also produced an embryo. In conclusion, measurement of serum AMH can be used to identify mares with higher chances of producing multiple in vitro embryos, but not as an independent predictor of successful OPU-ICSI in horses.

Association between GnRH Receptor Polymorphisms and Luteinizing Hormone Levels for Low Ovarian Reserve Infertile Women.

The choice of ovarian stimulation protocols in assisted reproduction technology (ART) cycles for low ovarian reserve patients is challenging. Our previous report indicated that the gonadotrophin-releasing (GnRH) agonist (GnRHa) protocol is better than the GnRH antagonist (GnRHant) protocol for young age poor responders. Here, we recruited 269 patients with anti-Müllerian hormone (AMH) < 1.2 ng/mL undergoing their first ART cycles for this nested case-control study. We investigated the genetic variants of the relevant genes, including follicular stimulating hormone receptor (FSHR; rs6166), AMH (rs10407022), GnRH (rs6185), and GnRH receptor (GnRHR; rs3756159) in patients <35 years (n = 86) and patients ≥35 years of age (n = 183). Only the genotype of GnRHR (rs3756159) is distributed differently in young (CC 39.5%, CT/TT 60.5%) versus advanced (CC 24.0%, CT/TT 76.0%) age groups (recessive model, p = 0.0091). Furthermore, the baseline luteinizing hormone (LH) levels (3.60 (2.45 to 5.40) vs. 4.40 (2.91 to 6.48)) are different between CC and CT/TT genotype of GnRHR (rs3756159). In conclusion, the genetic variants of GnRHR (rs3756159) could modulate the release of LH in the pituitary gland and might then affect the outcome of ovarian stimulation by GnRHant or GnRHa protocols for patients with low AMH levels.

An Exploration of the Reproductive Health Concerns in Women with Systemic Lupus Erythematosus

An Exploration of the Reproductive Health Concerns in Women with Systemic Lupus Erythematosus

Oligo/Amenorrhea Is an Independent Risk Factor Associated With Low Ovarian Response.

CapsuleOligo/amenorrhea is an independent risk factor of low ovarian response but not high ovarian response, particularly in women with low AMH levels.ObjectiveTo investigate the association of menstrual cycle length (MCL) with anti-Müllerian hormone (AMH) and ovarian response.MethodsThis was a retrospective cohort study. A total of 7471 women who underwent ovarian stimulation and oocyte retrieval were enrolled. The main outcome was the number of oocytes retrieved.Main ResultsA total of 5734 patients were eligible for analysis. In women without polycystic ovary syndrome (PCOS), serum AMH levels and antral follicle count were significantly lower in women with short cycles and higher in women with oligo/amenorrhea than those with a normal menstrual cycle. In women with PCOS, compared to women with a normal menstrual cycle, women with short cycles and women with oligo/amenorrhea showed higher antral follicle count and higher serum AMH levels. Compared with the 0-25th range group of AMH levels, 75-100th percentile groups showed a significantly increased rate of oligo/amenorrhea in women with and without PCOS [adjusted odds ratio (OR) =1.9 (1.04, 3.46), 2.4 (1.70, 3.35)]. In women without PCOS, the low ovarian response was more common in women with short cycles and less common in women with oligo/amenorrhea compared to women with normal cycles [OR=3.0 (2.38, 3.78), 0.7 (0.55, 0.96), respectively]. When adjusted for AMH levels, both short cycles and oligo/amenorrhea were associated with an increased risk of low response [adjusted OR=1.3 (1.02, 1.75), 1.3 (0.93, 1.86), respectively]. In women without PCOS and with low AMH levels, the low ovarian response was more common in women with short cycles as well as in women with oligo/amenorrhea [OR=1.5 (1.08, 1.98), 1.7 (1.08, 2.69), adjusted OR=1.2 (0.86, 1.74), 2.2 (1.31, 3.82), respectively].ConclusionAMH levels are significantly associated with increased risk of oligo/amenorrhea in women with and without PCOS. AMH is an indispensable confounder in the association between MCL and ovarian response in women without PCOS. Oligo/amenorrhea is an independent risk factor associated with a low ovarian response in women without PCOS, particularly those with low AMH levels.

Chemotherapy-induced ovarian failure in young women with early breast cancer: Prospective analysis of four randomised neoadjuvant/adjuvant breast cancer trials

BackgroundYoung women receiving chemotherapy for early breast cancer (EBC) have a high probability for ovarian failure, defined by chemotherapy-induced amenorrhea (CIA) as a surrogate. CIA is insufficiently reliable and reproducible. We analysed chemotherapy-induced ovarian failure (CIOF) by assessing hormone parameters, CIA, and antral follicle count (AFC). MethodsBlood samples of women aged ≤45 years treated with anthracycline/taxane-based chemotherapy for EBC from four neoadjuvant/adjuvant trials were collected at baseline, at the end of treatment (EOT), and at 6, 12, 18, and 24 months after EOT. Centrally assessed oestradiol (cutoff <52.2 ng/L) and follicle-stimulating hormone (cutoff >12.4IU/L) were used to define CIOF for patients with baseline premenopausal hormone levels, anti-Müllerian hormone (AMH), and AFC to assess ovarian reserve. Further analyses included CIA, regain of premenopausal hormone levels, and disease-free survival (DFS) also in subgroups. ResultsSix hundred ninety-six patients aged ≤45 years had premenopausal hormone levels at baseline. Overall, 85.1% (592/696) experienced CIOF at EOT, and 147 of 592 had further hormone measurements after EOT. Of those, 32.7% (48/147) regained premenopausal hormone levels after 6 months, 57.9% (66/114) regained premenopausal hormone levels after 12 months, 83.0% (73/88) regained premenopausal hormone levels after 18 months, and 89.2% (74/83) regained premenopausal hormone levels after 24 months. After 24 months, 72.4% (21/29) of patients without CIOF and 100% (14/14) with CIOF had low AMH levels. Four-year DFS without CIOF versus CIOF was 65.9% versus 84.6% (hazard ratio [HR] = 2.09, 95% confidence interval [CI]: 1.37–3.19; P < 0.001); in hormone receptor positive 61.8% versus 87.5% (HR = 2.69, 95% CI: 1.57–4.60; P < 0.001); in <30 years 68.3% versus 92.6% (HR = 4.87, 95% CI: 1.05–22.63; P = 0.026). ConclusionMost premenopausal women experienced CIOF after chemotherapy for EBC. After 2 years, nearly all regain premenopausal hormone levels. CIOF was associated with better DFS, especially in patients with hormone receptor–positive EBC or aged <30 years.

Low Anti-Mullerian Hormone Levels Are Associated with the Severity of Anxiety Experienced by Healthcare Professionals During the COVID-19 Pandemic.

The objective of this study is to investigate a possible correlation between anxiety status and anti-Mullerian hormone (AMH) levels among healthcare professionals who provide medical care directly to COVID-19-positive patients during the recent pandemic. Fifty-two healthcare professionals (nurses, midwives, and residents) who provide medical care directly to COVID-19-positive patients in inpatient clinics or intensive care units were enrolled in this study. Serum AMH levels were analyzed to reflect ovarian reserve. The Beck Anxiety Inventory (BAI) and the State-Trait Anxiety Inventory (STAI-S and STAI-T, respectively) were completed by participants to assess their anxiety status. A linear regression model with participant age as the constant variable was applied to analyze the relationship between inventory scale scores and AMH levels. P-values less than 0.05 were considered statistically significant. The mean AMH value was significantly lower for the participants in the moderate/severe anxiety group compared to the minimal/mild anxiety group (p = 0.007). A linear regression analysis revealed a significant negative correlation between AMH levels and both BAI (B = −0.030, standard error = 0.010, p = 0.004) and STAI-S and STAI-T scores when age was controlled (both p = 0.003). The severity of anxiety experienced during the recent COVID-19 pandemic among healthcare professionals, who provide medical care directly to COVID-19-positive patients, is found to be related to low AMH levels.

P173 Subfertility in young women and men patients with Crohn′s disease

Abstract Background Crohn’s disease (CD) affects young adults on reproductive age. They are likely to desire pregnancy and are often concerned about the potential effects of inflammatory bowel disease on fertility. Aims to investigate the effect of CD in fertility, studying the ovarian reserve in women by serum anti-Müllerian hormone (AMH) and Sertoli cell function in men measured by serum Inhibine (IB). Methods Cross-sectional, prospective, case-control study, including CD patients, aged 18–40 yr, and healthy controls(HC) matched by gender and age(ratio 2:1). Morning IB was measured using ELISA. Serum AMH was measured by ECLIA. Sociodemographic and phenotypic features of CD patients and controls were collected. We defined impaired fertility potential as IB level &amp;lt; 89 pg/mL and AMH &amp;lt;1.66 ug/L 0–24 yr, &amp;lt;1. 18 ug/L 25–29 yr, &amp;lt;0.67 ug/L 30–34 yr, &amp;lt;0.77 ug/L 35–39 yr, &amp;lt;0.01 ug/L 40–44 yr. AMH &amp;lt; 2 ug/L under 40 yr was considered low. Results A total of 122 subjects were included:73 men(48 CD, 25 HC) and 49 women(21 CD, 28 HC). No statistical difference was found between mean serum AMH levels in CD and HC women(2,23±1,8 vs 2,86±1,9 ug/L, p=0,5). The rate of abnormal serum AMH levels according to age did not differ between groups (19% CD vs 25% HC, p=0,4). When classified according to age(&amp;lt;30 and &amp;gt;30 yr), the serum AMH levels remained comparable in &amp;lt;30 yr (3.3±2.06 CD vs 3,2±1.96 ug/L HC, P=0.9). However, a low AMH level(&amp;lt;2 ug/L) was measured in 13 CD women(61%) and in 9 HC(32%)(P &amp;lt; 0.03), especially in&amp;gt;30 yr, 9 CD(90%)vs 4 in HC(40%)(p=0.02). Serum IB levels were significantly lower in CD men vs HC (175.4 ±62.3 vs 234.12±75.56 ug/L, p=0.002). We did not find abnormal IB(&amp;lt;89 pg/mL) in HC vs 3(6%) among CD men. Conclusion Women with CD did not have severe ovarian reserve alterations compared to a control population. However higher proportion of CD women showed low AMH (&amp;lt; 2 ug/L), especially those &amp;gt; 30 years. These data could be helpful for female CD patients who want to have children. Inhibine levels, as biomarker of Sertoli cell function, were lower in CD men compared to healthy controls.

Use of a high-sensitivity anti-Mullerian hormone (AMH) assay to determine ovarian function after chemotherapy for early breast cancer.

552 Background: It is now well established that AMH can indicate the extent of chemotherapy-induced damage on the ovarian reserve. Very low AMH levels in women after chemotherapy for early breast cancer (eBC) may indicate treatment-induced premature ovarian failure (POI), but the evidence to implement its routine clinical use remains limited. Methods: AMH was measured (Roche cobas autoanalyser) in 197 women aged 40-45 years at diagnosis treated with anthracycline/cyclophosphamide/taxane based chemotherapy for eBC, with no previous endocrine therapy and no subsequent aromatase inhibitor exposure or ovarian suppression. 76% were ER positive and received tamoxifen. The primary objective was to assess the relationships between AMH levels at 6 months after chemotherapy (AMH6) with subsequent ovarian function at 30 months. This included accuracy of prediction of loss of ovarian function at 30 months (E30) after chemotherapy by AMH levels at 6 months (AMH6) and the value of other endocrine/clinical factors pretreatment and at 6 months. Multivariate analysis was performed with data were split into 70% training and 30% testing sets with results reported for model performance on the test set. Results: AMH fell from a median of 0.62 (IQR 0.21-1.31) ng/ml pretreatment to become undetectable ( &lt; 0.01ng/ml) in 137 (70%) of women at 6 months. AMH showed very little recovery, being undetectable in 115 women at 18 months and 119 at 30 months. In those with detectable AMH at 30 months, it remained very low, median 0.07ng/ml, max 0.82ng/ml but nevertheless it reflected ovarian function. Thus median estradiol at 30 months (E30) was 50 pmol/l (IQR 34-68) in women with undetectable AMH at that time, vs 313 pmol/l (IQR 102-1052) in the 80 women with detectable AMH. AMH at 6 months was predictive of ovarian function at 30 months, as E30 was 56 pmol/l (IQR 40-104) in women with undetectable AMH6 vs 258pmol/l (IQR 69-780; p &lt; 0.0001) in women with detectable AMH6, and the positive predictive value (PPV) of AMH being undetectable at 6 months and remaining so at 30 months was 77%. Random forest analysis identified BMI as a non-endocrine predictive factor of E30. Using a stringent cutoff of ≤50pmol/l (13.6 pg/ml) and adding 1:9 weighting to improve PPV gave a test validated PPV of 79.0% while maintaining AUC at 83.7% for prediction of E30. Other classifiers performed less well than random forests. Conclusions: Measurement of AMH at 6 months after chemotherapy has predictive value for later ovarian function, and combining this with other endocrine and baseline data improves discriminative ability. This approach indicates the potential role of multivariate analysis based on AMH measured shortly after chemotherapy to helping optimise subsequent endocrine therapy.

Possible modification of BRSK1 on the risk of alkylating chemotherapy-related reduced ovarian function.

STUDY QUESTIONDo genetic variations in the DNA damage response pathway modify the adverse effect of alkylating agents on ovarian function in female childhood cancer survivors (CCS)?SUMMARY ANSWERFemale CCS carrying a common BR serine/threonine kinase 1 (BRSK1) gene variant appear to be at 2.5-fold increased odds of reduced ovarian function after treatment with high doses of alkylating chemotherapy.WHAT IS KNOWN ALREADYFemale CCS show large inter-individual variability in the impact of DNA-damaging alkylating chemotherapy, given as treatment of childhood cancer, on adult ovarian function. Genetic variants in DNA repair genes affecting ovarian function might explain this variability.STUDY DESIGN, SIZE, DURATIONCCS for the discovery cohort were identified from the Dutch Childhood Oncology Group (DCOG) LATER VEVO-study, a multi-centre retrospective cohort study evaluating fertility, ovarian reserve and risk of premature menopause among adult female 5-year survivors of childhood cancer. Female 5-year CCS, diagnosed with cancer and treated with chemotherapy before the age of 25 years, and aged 18 years or older at time of study were enrolled in the current study. Results from the discovery Dutch DCOG-LATER VEVO cohort (n = 285) were validated in the pan-European PanCareLIFE (n = 465) and the USA-based St. Jude Lifetime Cohort (n = 391).PARTICIPANTS/MATERIALS, SETTING, METHODSTo evaluate ovarian function, anti-Müllerian hormone (AMH) levels were assessed in both the discovery cohort and the replication cohorts. Using additive genetic models in linear and logistic regression, five genetic variants involved in DNA damage response were analysed in relation to cyclophosphamide equivalent dose (CED) score and their impact on ovarian function. Results were then examined using fixed-effect meta-analysis.MAIN RESULTS AND THE ROLE OF CHANCEMeta-analysis across the three independent cohorts showed a significant interaction effect (P = 3.0 × 10−4) between rs11668344 of BRSK1 (allele frequency = 0.34) among CCS treated with high-dose alkylating agents (CED score ≥8000 mg/m2), resulting in a 2.5-fold increased odds of a reduced ovarian function (lowest AMH tertile) for CCS carrying one G allele compared to CCS without this allele (odds ratio genotype AA: 2.01 vs AG: 5.00).LIMITATIONS, REASONS FOR CAUTIONWhile low AMH levels can also identify poor responders in assisted reproductive technology, it needs to be emphasized that AMH remains a surrogate marker of ovarian function.WIDER IMPLICATIONS OF THE FINDINGSFurther research, validating our findings and identifying additional risk-contributing genetic variants, may enable individualized counselling regarding treatment-related risks and necessity of fertility preservation procedures in girls with cancer.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by the PanCareLIFE project that has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 602030. In addition, the DCOG-LATER VEVO study was funded by the Dutch Cancer Society (Grant no. VU 2006-3622) and by the Children Cancer Free Foundation (Project no. 20) and the St Jude Lifetime cohort study by NCI U01 CA195547. The authors declare no competing interests.TRIAL REGISTRATION NUMBERN/A.

Controlled ovarian hyperstimulation for poor ovarian responders undergoing in vitro fertilisation/intracytoplasmic sperm injection: a protocol for systematic review and Bayesian network meta-analysis

IntroductionControlled ovarian hyperstimulation (COH) is the routine regimen used to generate a sufficient number of follicles during in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatment. Poor ovarian response...

Is low anti-Mullerian hormone (AMH) level a risk factor of miscarriage in women

Anti-Mullerian Hormone (AMH) is considered to be one of the most relevant markers of ovarian reserve. However, its association with oocyte quality, pregnancy occurrence and evolution remain to be further investigated. The objective of this study was to compare miscarriage rate after fresh blastocyst(s) transfer in young women (<37 years old) with or without diminished ovarian reserve (DOR), as reflected by low serum AMH levels. This monocentric retrospective study was conducted in 669 women undergoing 1,891 blastocyst transfers. Patients were divided into 2 groups: (1) 190 transfers performed in 106 women with a ‘low’ serum AMH (< 10th percentile) (i.e. AMH < 0.85 ng/mL); and (2) 961 transfers performed in 563 patients with a ‘normal’ serum AMH (25th–75th percentile) (i.e. AMH 1.4–4 ng/mL). Miscarriage rate was comparable in both groups (9.5 and 6.8% respectively; p = 0.2) as well as implantation rate, pregnancy rate, live birth rate per transfer (p = 0.4, p = 0.07 and p = 0.6, respectively). After multivariate analysis, no significant association was found between serum AMH level and miscarriage rate (p = 0.22). In women <37 years, low serum AMH level is not associated with an increase in miscarriage rate after fresh blastocyst transfer.

Use of Anti-Mullerian Hormone (AMH) for Testing of Ovarian Reserve: A Survey of Fifteen (15) Fertility Centres in Ghana

Anti-Mullerian Hormone (AMH) is a dimeric glycoprotein with a molecular weight of 140 kD, encoded by a gene on the short arm of chromosome and a member of the transforming growth factor-beta (TGF-β) superfamily. The expression of AMH is markedly different in males and females, both in concentration and temporality. In males, Sertoli cells maintain a high concentration of AMH in utero which peaks shortly after birth and then drops precipitously at puberty. In females, granulosa cells produce very low levels of AMH in utero followed by a transient spike in the neonatal period. Concentrations of the hormone then rise steadily through adolescence to a peak in the mid-twenties and subsequently decline until becoming undetectable in menopause. The study aimed to understand how Clinicians and Clinical Embryologists used anti-mullerian hormone (AMH) test to assess ovarian reserve, direct patient selection and treatment regimens and guide in vitro fertilization (IVF) cycle management in all registered fertility hospitals in a West African country, Ghana. A web-based survey (questionnaire) using google forms was performed to solicit responses from all IVF hospitals that are registered with the Fertility Society of Ghana (FERSOG). This questionnaire consisted of fifteen (15) broader questions, ten (10) of which assessed the clinics’ use of AMH. Responses were screened for quality to verify that only one (1) survey was completed by each IVF centre. The study was conducted during May and June 2020 at the In Vitro Fertilization (IVF) Department of the Airport Women’s Hospital (AWH) in Accra, Ghana. Results are reported as the proportion of IVF cycles represented by a particular answer choice. Survey responses were completed from 15 IVF centres, representing 2504 IVF cycles performed annually. A good majority (73.3%) [1835 IVF cycles] of the respondent IVF hospitals reported to use AMH as a first line test and 93.3% reported it as the best test for evaluating ovarian reserve. Another 66.7% reported that AMH results were extremely relevant to clinical practice. However, in contrast, for predicting live birth rate, 60% reported age as the best predictor in their practice. Overall, our results indicate that AMH is considered a first line test for assessing ovarian reserve and is relevant to the clinical practice of majority of Assisted Reproductive Technologies (ART) providers in Ghana.

Live birth outcomes from IVF treatments in younger patients with low AMH.

Objective:Anti-Müllerian hormone (AMH) is used to predict in vitro fertilization outcomes. However, predicting live birth is difficult in younger patients with low AMH. Thus, this study aimed to determine the live birth rates from younger patients with low anti-Müllerian hormone levels.Methods:A total of 296 infertile patients with AMH measured (younger group, aged 25-38 years; older group, aged 39-42 years) were included in this study. In vitro fertilization outcomes between patients with AMH levels of <1.0ng/mL and ≥1.0ng/mL were compared.Results:Younger patients with AMH levels <1.0ng/mL (younger low AMH group) exhibited lower number of oocytes retrieved than patients with AMH levels ≥1.0ng/mL (younger normal AMH group). However, there were no significant differences in cumulative pregnancy or cumulative live birth rates between groups. Older patients with AMH levels ≥1.0ng/mL (older normal AMH group) had significantly better outcomes as per mean number of oocytes, cumulative pregnancy rate, and cumulative live birth rate than older patients with AMH levels <1.0ng/mL (older low AMH group). In the younger low AMH group, the frequency of oocyte retrieval was significantly higher in patients who achieved live birth. In addition, the blastocyst transfer rate was significantly higher in individuals with live births versus subjects with non-live births.Conclusions:AMH is a predictor of live birth among older, but not younger, women. Our report suggests that younger women may become pregnant even with low AMH levels when they obtain blastocysts from frequent oocyte retrievals.

AMH Concentrations in Peritoneal Fluids of Women With and Without Endometriosis.

Background: As its name indicates, anti-Müllerian hormone (AMH) is primarily found as an inhibitor of the Müllerian duct in male fetus. On the other hand, AMH may act as a mediator of Müllerian duct-derived female tissue, such as endometrium in normal and pathological conditions. However, the role of AMH in the functional regulations of endometriosis is not well understood. It can be hypothesized that AMH in peritoneal fluids may affect the activity of peritoneal endometriosis. In this study, we investigated the levels of AMH in peritoneal fluids (PF) in women with and without endometriosis.Methods: PF were collected during laparoscopy from 90 women diagnosed as having advanced endometriosis (rASRM stage III, n = 30; stage IV, n = 60), and 32 women without endometriosis were served as control. Paired serum samples were also collected before the surgery. AMH in PF and serum were measured by ELISA. Individual clinical information was collected. AMH levels were compared according to the presence of endometriosis. The expression of AMHR2 in peritoneal endometriotic lesions obtained during laparoscopy was examined by immunohistochemistry.Results: AMH levels in PF were positively and significantly correlated with serum AMH levels in both women with and without endometriosis (R2 = 0.17, P < 0.0001; R2 = 0.30, P = 0.001, respectively). Serum AMH levels were inversely and significantly correlated with age in women with endometriosis (R2 = 0.092, P = 0.004) and in control women without statistical significance (R2 = 0.078, P = 0.12). AMH levels in PF were also inversely but not significantly correlated with age in women with and without endometriosis (R2 = 0.029, P = 0.11 and R2 = 0.027, P = 0.37, respectively). Mean age and serum AMH levels were not significantly different between two groups. On the other hand, AMH levels in PF were significantly lower in women with endometriosis compared to those of control women [2.15 ± 2.13 (mean ± SD) vs. 4.40 ± 4.77 ng/mL, P = 0.0001]. AMHR2 are localized at glandular epithelium and stromal cells in the ectopic endometrium of peritoneal endometriosis.Conclusions: Women with endometriosis may present lower PF AMH levels even if they retain serum levels similar to women without disease. As peritoneal endometriosis expresses a specific receptor for AMH, lower AMH levels in PF of women with advanced endometriosis may be involved in the pathophysiology of peritoneal endometriosis.

Learning to listen: how empathetic engagement with patients can help overcome reproductive injustice

Dialogue for paper: Anti-Mullerian Hormone in African American Women with Systemic Lupus Erythematosus Reproductive justice stands at the intersection of social justice and reproductive health, where it focuses attention on...

Air pollution and anti-Müllerian hormone concentrations in the Sister Study

Background: Anti-Müllerian hormone (AMH) levels are a marker of ovarian reserve and are indicative of a woman’s reproductive life span. Although exposure to indoor air pollution has been associated with diminished AMH, little is known about the association between ambient air pollution and ovarian reserve especially in a population not seeking fertility treatments. Methods: For 4,696 Sister Study participants, residential annual average exposure to PM2.5, PM10 , and NO2 was assessed using land-use regression models and kriging. We estimated distance to the nearest major road for both adult and childhood residences. Serum AMH was measured using ultrasensitive AMH ELISA and picoAMH ELISA kits in 1,322 premenopausal women. We also included postmenopausal women (N = 3,374) in our analyses to address potential selection bias. Inverse probability weighting was used to account for selection into the study. For postmenopausal women or women with AMH values below the limit of detection (LOD), AMH values were imputed as LOD/2. To account for the non-detects, reverse Cox regression modeling with restricted cubic spline adjustment for age was used to estimate hazard ratios (HRs) for the association between ambient air pollution and distance to major roadway and AMH levels. Results: Overall, we saw no consistent association between air pollution exposure or proximity to roadways and AMH levels. An interquartile range (IQR) increase in NO2 was associated with slightly higher AMH levels (HR = 1.10, 95% CI: 0.99, 1.22). However, among the women not currently using oral contraceptives (which may impact measured AMH levels), an IQR increase in PM2.5 was associated with lower AMH levels (HR = 0.88, 95% CI: 0.77-0.99). Conclusions: We saw little evidence to support an association between outdoor air pollution and diminished ovarian reserve in women of older reproductive age, except possibly among women who were not current users of hormonal contraceptives.

Extracellular vesicles miRNA-21: a potential therapeutic tool in premature ovarian dysfunction.

Chemotherapy induces an irreversible premature ovarian dysfunction (POD). Amniotic fluid mesenchymal stem cells (AFMSCs) can rescue fertility; however, the notion that stem cells can rejuvenate follicles is highly controversial due to the predetermined ovarian reserve. This study aims to isolate AFMSC-derived extracellular vesicles (EVs) and investigate their abundancy for the anti-apoptotic miRNA-21 as a means of ovarian restoration. Female rats were divided into healthy controls and POD-induced groups. The POD induced groups were subdivided into three groups according to the therapies they received: placebo-treated POD, AFMSC and EVs groups. Rats were assessed for serum anti-Müllerian hormone (AMH) levels, ovarian caspase 3 and PTEN protein levels in the ovarian lysate. Total follicular counts (TFCs) were estimated from stained ovarian sections. Functional recovery was investigated through daily vaginal smears and mating trials. In vitro chemical transfection of the AFMSCs with selective miRNA-21 mimics/inhibitors followed by isolation of EVs for therapy was conducted in two additional groups. At the interval points studied, treatment with AFMSCs and EVs equally restored TFC, AMH levels, regular estrous cycles and fruitful conception, while it both diminished caspase 3 and PTEN levels. EVs carrying miRNA-21 mimics recapitulated the short-term effects. Placebo-treated POD or EVs carrying miRNA-21 inhibitors showed augmented ovarian follicular damage demonstrated the low AMH levels, TFC and high levels of PTEN and caspase 3. miRNA-21 allowed regeneration by modulating PTEN and caspase 3 apoptotic pathways. Our findings exemplify that EVs could serve as an innovative cell-free therapeutic tool functioning through their miRNA content and that miRNA-21 has a chief regenerative role through modulating PTEN and caspase 3 apoptotic pathways.

Elevated levels of nitrous dioxide are associated with lower AMH levels: a real-world analysis.

Are there any associations between environmental pollutants and ovarian reserve, expressed by anti-Mullerian hormone (AMH) serum levels? In this first real-world approach to demonstrate the relationship between air pollutants and serum AMH levels, adverse associations were observed for nitrogen dioxide (NO2) but not with particulate matter. In recent years, air pollution has emerged as a potential disrupter to the homeostasis of physiological hormones, possibly affecting human reproduction. Although the influence of age and smoking on AMH levels is largely accepted, the relationship between AMH and the environment has not currently been established. A longitudinal, observational, retrospective, real-world study was carried out, including all AMH measurements performed in a single laboratory from January 2007 to October 2017. Serum AMH data were connected to patients' age and residential address, to include air pollution data after geo-localisation. The air pollution considered daily particulate matter (PM) and NO2 values. A total of 1463 AMH measurements were collected (mean 1.94 ng/ml, median 0.90 ng/ml). AMH was inversely related to patients' age in women older than 25 years (adjusted R-squared 0.120, P < 0.001), but not in those younger than 25 years (adjusted R-squared 0.068, P = 0.055). AMH levels were inversely related to environmental pollutants, such as PM10 (Rho = -0.088, P = 0.001), PM2.5 (Rho = -0.062, P = 0.021) and NO2 (Rho = -0.111, P < 0.001). After subdividing the dataset into quartiles for PM10 and PM2.5, the influence of age on AMH serum levels was found to be a stronger influence than that exerted by PM (P = 0.833 and P = 0.370, respectively). On the contrary, considering NO2 quartiles, higher AMH levels were observed in third quartile compared to fourth quartile, even after adjustment for age (P = 0.028), indicating a stronger influence of NO2 exposure on AMH serum levels. Considering an AMH cut-off of 0.3 ng/ml, a significant higher frequency of women with severe ovarian reserve reduction in the fourth quartile was shown only for NO2 (P = 0.010). Several limitations should be underlined, such as the lack of information about work and life habits of each patient and the retrospective nature of the analysis performed on real-world data. Although the genetic component is highly predictive for defining the ovarian reserve at birth, potentially modifiable environmental factors could influence the rate of decline in AMH and ovarian reserve during adulthood. Authors have neither funding nor competing interests to declare. N/A.

Evolution of serum Anti-Müllerian Hormone (AMH) level in young women treated with chemotherapy for breast cancer according to basal AMH level

ObjectiveSerum AMH level has been shown to decrease in women treated for breast cancer in several studies. However, whether basal AMH status affects AMH dynamics during chemotherapy remains to be clarified. The objective of this study was to compare serum AMH dynamics in young women with either low, normal or high basal serum AMH level at diagnosis, during and after treatment with chemotherapy for breast cancer. Study designIn this secondary analysis of a prospective cohort study, serum AMH was measured during and after chemotherapy in 239 women of reproductive age diagnosed with breast cancer and treated with chemotherapy. The association between AMH dynamics throughout chemotherapy and during follow-up and basal AMH status, i.e. low AMH (<1 μg/l, <7 pmol/l), normal AMH (1–4.9 μg/l, 7−36 pmol/l) and high AMH (≥5 μg/l, >36 pmol/l), was evaluated. Menses occurrence was also recorded. ResultsA total of 21 women had low, 154 had normal and 64 had high basal AMH level. Serum AMH rapidly decreased during chemotherapy in all groups, and its variation during chemotherapy and follow-up was not significantly different between the 3 groups. ConclusionNo association was found between AMH variation during chemotherapy and follow-up, and basal AMH level at diagnosis. However, women with high basal AMH levels have significantly higher AMH levels throughout chemotherapy and follow-up than women with normal or low basal AMH levels at diagnosis.

Very Low Levels of Serum Anti-Müllerian Hormone as a Possible Marker for Follicle Growth in Patients with Primary Ovarian Insufficiency Under Hormone Replacement Therapy.

Patients with primary ovarian insufficiency (POI) occasionally present with follicle growth; however, accurately predicting cycles accompanied by follicle growth is challenging. Early-stage follicles produce serum anti-Müllerian hormone (AMH), a useful marker of ovarian reserve. Therefore, serum AMH levels indicate growth of small follicles (which are difficult to detect ultrasonographically) and may predict follicle growth in patients with POI. Using an ultrasensitive enzyme-linked immunosorbent assay (ELISA) kit, we observed very low serum AMH levels in patients with POI. We further evaluated follicle growth in each patient during each cycle to determine the usefulness of measuring serum AMH levels as a predictor of follicle growth in patients with POI who receive hormone replacement therapy (HRT). We investigated 19 patients with POI in whom we analyzed 91cycles; 14cycles showed positive and 77cycles showed negative results on serum AMH testing. The rate of cycles showing follicle growth in AMH-positive cycles was higher than that in AMH-negative cycles (64.3% vs. 6.5%, p = 0.0001). The median serum AMH level (7.7pg/mL [25th and 75th percentiles 4.6pg/mL and 22.3pg/mL, respectively]) in AMH-positive cycles was lower than the lower limit of detection of conventional AMH ELISA kits. The positive predictive value of positive serum AMH levels for follicle growth was higher than that of follicle-stimulating hormone (< 10mIU/mL). These results indicate that a very low level of serum AMH detected using picoAMH assays is a useful predictor of follicle growth in patients with POI receiving HRT.